ABSTRACT: Background. Semisynthetic coating of the Camouflage bare-metal stent (BMS) (Eucatech AG, Rheinfelden, Germany) mimics luminal endothelial cell glycocalix, potentially preventing the activation of the coagulation system. Purpose. We sought to determine in a clinical registry the acute and long-term clinical and angiographic outcomes of this BMS design in patients with acute coronary syndromes (ACS) or who were unable to be on long-term clopidogrel therapy. Methods. From March 2007 to December 2008, 150 patients undergoing coronary stent implantation at three centers in Buenos Aires, Argentina, were included in our registry. Patients with ACS, including non-ST-elevation myocardial infarction (NSTEMI) and ST-elevation MI (STEMI), or those unable to be on long-term dual antiplatelet therapy were considered for inclusion. The primary endpoint was a major adverse cardiovascular event (MACE) defined as the incidence of cardiac death, MI or target lesion revascularization (TLR). The incidence of acute and late stent thrombosis (ST) was also analyzed. Angiographic late loss and the presence of late stent malapposition (LSM) was recorded at 9-month follow up. Clopidogrel was prescribed for 1 month. Results. 54.7% of patients had acute MI, 36% had STEMI and 20.7% of patients were ineligible for long-term clopidogrel therapy because of previously planned non-vascular or general surgery within 30 days after percutaneous coronary intervention. During 11.5 months of clinical follow up, 2% suffered cardiac death, 4% had a MI, 8.9% underwent TLR and the overall cumulative major adverse cardiac event rate was 15.3%. No patient developed acute or late ST. There were no in-hospital complications for patients who underwent surgery. Intravascular ultrasound studies did not detect the presence of late malapposition. Conclusion. In this high-risk thrombotic patient population, the Camouflage coated stent design demonstrated a very good safety profile, as reflected by the low incidence of hard adverse cardiac events including ST at follow up.
J INVASIVE CARDIOL 2009;21:378–382
The introduction of drug-eluting stents (DES) in clinical practice dramatically reduced the incidence of angiographic and clinical restenosis rate.1-4 However, a number of queries related to off-label indications of these devices remained.5–7 Previous studies have shown that patients treated with DES during acute coronary syndromes (ACS), especially those with ST-segment-elevation myocardial infarction (STEMI), have had a higher incidence of adverse events at follow up, either reinfarction or stent thrombosis,8,9 particular those with a large thrombus burden.10 In addition, it is well known that coronary stent implantation with either bare-metal stents (BMS) or DES was associated with a higher rate of adverse events when patients underwent general or vascular noncardiac surgery within the first 30 days after the stent procedure.11,12 The use of a dedicated stent specially designed to improve safety outcomes in the above clinical situations is the next challenge for the new generation of stents, whether BMS or DES designs.
We report here the acute and 12-month outcomes in patients included in a multicenter registry on the use of the Camouflage BMS (Eucatech AG, Rheinfelden, Germany), which is covered by a semisynthetic coating that mimics the endothelial surface.
Methods
Patient population. From March 2007 to November 2008, 1,629 patients with clinical indications for coronary angiography and myocardial revascularization were analyzed, 1300 of whom were selected for percutaneous coronary intervention (PCI); 150 of these (9.2% of the initial group) met the clinical and angiographic criteria for inclusion in the registry and were treated with a Camouflage stent. Coronary angioplasty was performed at the catheterization facilities of the Sanatorio Otamendi, Clinica IMA and Sanatorio Las Lomas in Buenos Aires, Argentina (Figure 1).
Inclusion criteria. Patients were included if they had a clinical indication for myocardial revascularization, age > 18 years, de novo severe stenosis suitable for stenting (≥ 70% visual estimation), reference vessel size between 2.5 mm and 4.0 mm by visual estimation, and if the patients were also suitable for coronary bypass surgery (CABG). High-risk thrombotic lesions were defined either by the presence of ACS including unstable angina Braunwald Class III-B or C, non-ST-segment elevation myocardial infarction (NSTEMI) or STEMI. Patients with other types of unstable angina or stable angina were included only if they had scheduled a noncardiac general or vascular surgery during the first 30 days after stent deployment. Patients with lesions in a saphenous bypass graft were also included. In-stent restenotic lesions, reference vessel size 3 times the upper limit of normal (ULN), with a concomitant increase in the MB isoenzyme. TLR and TVR were performed only when clinically indicated.
Coronary angioplasty and stent deployment. Coronary angioplasty was performed using the standard techniques previously described.13 Stenting of the target lesion was accomplished using the Camouflage coated stent as the primary device. The Camouflage stent is a slotted-tube, open-cell design with a strut thickness of 0.0033 µm, and a dense semisynthetic coating that mimics endothelial cell glycocalix. Contrary to heparin, for which the antithrombotic activity is related to a highly specific sulfation pattern, this coating lacks such binding sites and does not provide excessive negative charges to coated surfaces, thereby avoiding activation of the coagulation system. Biomimicry of cell membrane glycocalyx serves as a model for a nonthrombogenic interface. Glycocalyx is composed of dense, highly hydrated polysaccharides that create a repulsive barrier against the nonspecific absorption of plasma proteins, avoiding the initiation of the coagulation cascade.
After stent deployment, high pressure up to 13 atm was used in all patients. Patients were treated with aspirin (500 mg) and a bolus of 600 mg of clopidogrel. Heparin was given intravenously to achieve an activated clotting time of > 300 seconds. After PCI, dual antiplatelet therapy was prescribed for 30 days. For patients undergoing noncardiac vascular or general surgery soon after PCI (within the next 30 days), antiplatelet therapy was discontinued 5 days before the surgical procedure. All patients were followed clinically for 1 year and a subgroup of 50 patients were scheduled for angiographic follow up at 9 months, 20 of whom also underwent an intravascular ultrasound (IVUS) study.
The protocol was approved by the medical and ethical committees of each of the three participating hospitals in the registry and also for the ethics and safety committees of the Cardiovascular Research Center. The study was conducted according to the principles of the Declaration of Helsinki, and all patients signed a written informed consent for participation in this trial. The Cardiovascular Research Center, a nonprofit organization, was in charge of the trial’s management, the accuracy of the data analyses and the completeness of the material reported.
Quantitative angiographic data. Coronary angiograms obtained at baseline, after completion of the stenting procedure and at late follow up were digitally recorded and analyzed by a central core lab by an independent observer. The analysis was performed using automated edge-detection software (CMS, Medis Medical Imaging Systems, Leiden, the Netherlands) at a single projection showing the most severe stenosis. The same projection was used at follow up. The proximal and distal edges were evaluated up to 5 mm from the stent.
IVUS imaging and analysis. IVUS analysis was obtained only at follow up to determine the presence of stent malapposition. Procedural and periprocedural IVUS data were not collected. IVUS imaging was performed with motorized pullback (0.5 mm/sec) starting at least 10 mm distal to the stent, ending at the coronary ostium. A 2.9 Fr 20 MHz catheter and one of the commercially available systems was used (Atlantis, Galaxy, Boston Scientific Corp., Natick, Massachusetts). Before imaging, 200–300 µg of intracoronary nitroglycerin were administered. The external elastic membrane, cross-sectional area (CSA) and lumen CSA of segments 5 mm proximal and distal to the stent were determined per frame, as were vessel volume, mean lumen area and minimal lumen area. The stented segment (5 mm proximal and distal to the stent) was analyzed. In cases of malapposition, the stent boundaries were used as lumen boundaries. Stent malapposition was defined as a separation of at least 1 stent strut, not overlapping a side branch, from the intimal surface with IVUS evidence of blood speckles behind the strut.14 The site of malapposition was classified as: 1) the body of the stent; 2) the proximal stent edge; or 3) the distal stent edge. Only patients with MI (STEMI and NSTEMI) were selected for IVUS follow-up analysis.
Statistical analysis. Statistical analysis was performed using SPSS software, version 11.0.5 (SPSS, Inc., Chicago, Illinois). Continuous variables were expressed as mean (standard deviation [SD]). Univariate and multivariate Cox regression analysis was performed (intro mode: all variables introduced in block in a single step) to determine independent predictors of poor outcome at follow up (MACE and TLR). Variables of statistical significance after univariate analysis and clinically relevant covariates including all demographic, clinical, angiographic and procedural variables were included in the analysis. A p-value Results
Table 1 describes baseline demographic and clinical characteristics of patients included in the registry. The mean age was 63 years. Diabetes was found in 13.4% of participants, peripheral vascular disease in 6.7%, previous MI in 23%, family history of coronary artery disease in 15.3% and previous cardiovascular accident in 3.4%. Almost 80% had ACS, 36% with STEMI, 43.3% either with NSTEMI or unstable angina IIIb or C, and 20.6% were unable to take clopidogrel due a previously scheduled noncardiac vascular or general surgery soon after stent deployment; 10 of these patients stopped clopidogrel at the second week after PCI, and for 21 patients, clopidogrel was discontinued 15–30 days after stent deployment. Multivessel disease was present in 68% of patients, with left main stenosis in 7.3% of these. Of these 150 patients, we treated 179 lesions with 184 stents (1.23 stent per patient). Procedural and angiographic data are described in Table 2.
Procedural and in-hospital results. During the initial procedure, 1 patient died due to unsuccessful PCI, another patient with cardiogenic shock who underwent primary PCI for STEMI died 30 days after the initial procedure due to multiple organ failure. Three patients had an abnormal enzyme rise after PCI. One NSTEMI patient and 2 STEMI patients underwent an emergent, new PCI to treat side-branch closure. Overall procedural and hospital MACE was 3.3% (Table 3).
Follow-up results. All patients were clinically followed by personal interview during 11.5 ± 6.1 months. Out of hospital, 1 patient died after coronary artery bypass graft (CABG) surgery to treat in-stent restenosis. Three additional patients suffered recurrent MI, 2 had NSTEMIs and 1 had a STEMI after CABG to treat in-stent restenosis. TVR was 9.7% and TLR was 8.4%. Cumulative events (hospital and follow up) are described in Table 3. The incidence of cardiac death was 2.0%, MI was 4%, TVR and TLR were 10.4% and 8.9%, respectively, with an overall MACE rate at 12.4 months of 15.3%. Of note, in the subgroup of 31 patients undergoing general or noncardiac surgery during the next 30 days after stent deployment, no adverse events occurred in the acute hospital phase.
Quantitative angiographic and IVUS data. During follow up, 38 asymptomatic and 16 symptomatic patients underwent follow-up angiography, 42 patients from the initial 50 previously selected for the re-study angiogram (84%). Quantitative angiographic data are described in Table 4. Late loss was 0.83 mm in the overall population and 0.45 mm in the asymptomatic patients. Of the 82 acute MI patients included in the registry, 20 underwent an IVUS substudy at follow up. In 1 of these patients who had severe restenosis, we were unable to cross the tight lesion, thus good IVUS quality was achieved in 19 of the 20 patients. LSM was not detected in any of the stents deployed during the initial PCI procedure.
Multivariate predictors of outcome. Univariate analysis identified that family history, high cholesterol, cardiovascular accident and lesion characteristics were high-risk predictors of an adverse outcome. The variables analyzed in the model were sex, age, family history of coronary artery disease, hypertension, diabetes, high cholesterol, renal failure, smoking habit, angina status, unstable angina, previous acute MI, previous PCI, previous stroke, multivessel disease, left anterior descending artery disease, left main stenosis, number of treated vessels, lesion characteristics, number of treated lesions, number of stents and stent length.
Multivariate analysis of the predictors of MACE showed that family history of previous coronary disease was the only independent predictor associated with MACE at follow up (p = 0.042; odds ratio [OR] 0.28, confidence interval [CI] 95% 0.087–0.95). In addition, a Class C lesion was the only independent predictor associated with a trend toward a high rate of TLR at follow up (p = 0.064; OR 0.23, CI 0.052–1.08).
Discussion
This prospective, observational multicenter registry in lesions defined clinically as high risk for thrombosis and adverse clinical events, the use of a dedicated Camouflage BMS covered with a dense semisynthetic coating that mimics endothelial cell glycocalix demonstrated safety outcome either acute or long term. This was also determined by the absence of ST by any definition. Furthermore, the subgroup of patients undergoing noncardiac or general surgery within the first 30 days after stent deployment had a zero percent incidence of hard clinical adverse events during the surgical procedure, including the hospitalization recovery period.
It is well known that this last cohort of patients is a subgroup at high risk ST and adverse cardiac events, regardless of stent design. Furthermore, when patients have undergone surgery Conclusion
In conclusion, this prospective, consecutive, multicenter and observational registry of patients defined as high risk for thrombotic complications demonstrated a very good short- and long-term safety profile confirmed by the low incidence of hard clinical endpoints including any definition of ST. However, cost-effectiveness data in comparison with other stent designs including DES are pending and require future randomized studies.
From the *Cardiac Unit Sanatorio Otamendi, Sanatorio las Lomas and Clinica IMA, and §Cardiovascular Research Center (CECI), Buenos Aires, Argentina.
Disclosures: Investigators received $500 U.S. dollars for each patient included in the registry. Fees were provided by Eucatech AG. In addition, IVUS catheters for IVUS follow-up studies were provided free of charge.
Manuscript submitted February 11, 2009, provisional acceptance given March 17, 2009, final version accepted March 24, 2009.
Address for correspondence: Alfredo E Rodriguez, MD, PhD, FACC, FSCAI, Callao 1441 4B (1024), Capital Federal, Buenos Aires, Argentina. E-mail: rodrigueza@sanatorio-otamendi.com.ar
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